US 12,281,138 B2
5′-cap-trinucleotide- or higher oligonucleotide compounds and their use in stabilizing RNA, expressing proteins in therapy
Andreas Kuhn, Mainz (DE); Hiromi Muramatsu, Mainz (DE); Katalin Kariko, Mainz (DE); Stephanie Fesser, Mainz (DE); and Ugur Sahin, Mainz (DE)
Assigned to BioNTech RNA Pharmaceuticals GmbH, Mainz (DE)
Appl. No. 16/980,300
Filed by BioNTech RNA Pharmaceuticals GmbH, Mainz (DE)
PCT Filed Mar. 14, 2019, PCT No. PCT/EP2019/056502
§ 371(c)(1), (2) Date Sep. 11, 2020,
PCT Pub. No. WO2019/175356, PCT Pub. Date Sep. 19, 2019.
Claims priority of application No. PCT/EP2018/056595 (WO), filed on Mar. 15, 2018.
Prior Publication US 2021/0363172 A1, Nov. 25, 2021
Int. Cl. C07H 21/02 (2006.01); A61K 31/7125 (2006.01); A61K 48/00 (2006.01)
CPC C07H 21/02 (2013.01) [A61K 31/7125 (2013.01); A61K 48/005 (2013.01)] 69 Claims
 
1. A 5′-cap compound having the 5′-cap structure according to formula (I):

OG Complex Work Unit Chemistry
wherein R1 is selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl;
R2 and R3 are independently selected from the group consisting of H, halo, OH, and optionally substituted alkoxy, or R2 and R3 together form O—X—O, wherein X is selected from the group consisting of optionally substituted CH2, optionally substituted CH2CH2, optionally substituted CH2CH2CH2, optionally substituted CH2CH(CH3), and optionally substituted C(CH3)2, or R2 is combined with the hydrogen atom at position 4′ of the ring to which R2 is attached to form —O—CH2— or —CH2—O—;
R4 and R6 are independently selected from the group consisting of O, S, Se, and BH3;
R5 is selected from the group consisting of S, Se, and BH3;
R7 is a mononucleotide or an oligonucleotide having 2 to 9 bases;
R8 is H, halo, or optionally substituted alkoxy;
n is 1, 2, or 3; and
B is a purine or pyrimidine base moiety;
wherein the 5′-cap compound is capable of co-transcriptional incorporation into an RNA strand.